Angiotensinase activity in mice fed an olive oil-supplemented diet

We evaluated the influence of a diet supplemented with olive oil (20% by weight) (OO) on the activity of glutamyl aminopeptidase (GluAP) and aspartyl aminopeptidase (AspAP), which are involved in angiotensin metabolism. Serum concentrations of total cholesterol and fatty acids were also measured. Animals fed on the OO diet gained significantly more weight than did controls from the second week until the end of the feeding period. Serum total cholesterol concentration was significantly higher in the OO group than in control mice. Total monounsaturated fatty acids increased in OO-fed animals, but total saturated fatty acids decreased. No differences between the two groups were observed for total polyunsaturated fatty acids. Serum from animals fed on the OO diet contained significantly lower proportions of myristic, pentadecanoic, palmitic, palmitoleic, vaccenic, alpha-linolenic, gamma-linolenic, and 11,14-eicosadienoic acids than did serum from control animals. In contrast, the OO group had higher levels of oleic, stearic, and gondoic acids. GluAP activity decreased significantly in the serum of OO-fed animals. In these animals soluble AspAP activity was significantly higher in the testis, and significantly lower in the lung and adrenal, in comparison to controls. Membrane-bound AspAP activity was higher in the testis and atrium, and lower in lung, in the OO group. Soluble GluAP activity was significantly lower in the testis of OO-fed animals. Membrane-bound GluAP activity did not differ between the two groups in any of the tissues analyzed. Serum AspAP and GluAP activities correlated negatively with palmitoleic and vaccenic acid respectively in the OO group. However, no significant correlations were found in the control group. These results may reflect functional changes in the renin-angiotensin system in the serum, adrenal, testis, lung and atrium after feeding with a diet enriched in olive oil.     

Metabolic fate of milk glycosaminoglycans in breastfed and formula fed newborns

In this study, the content, structure and residual percentages of glycosaminoglycans (GAGs) in the feces of seven breastfed newborns after ingesting a known amount of milk were studied. A comparison was made with five newborns fed with formula milk. Characterization of GAGs from milk and feces samples was performed according to previous methodology. Compared to the ingested GAGs present in milk, residual feces GAGs of breastfed newborns were <0.4 %, contrary to formula milk fed children, where the residues were ~4 %. As a consequence, >99 % of human milk GAGs are utilized as opposed to ~96 % of formula milk. Hyaluronic acid utilization was found to be fairly similar contrary to chondroitin sulfate/dermatan sulfate and heparan sulfate, which were found to be ~10–18 times lower in formula milk fed children. Our new results further demonstrate that the elevated content of human milk GAGs passes undigested through the entire digestive system of newborns, possibly protecting the infant from infections. In the distal gastrointestinal tract, these complex macromolecules are catabolized by a cohort of bacterial enzymes and constituent monosaccharides/oligosaccharides utilized for further metabolic purposes potentially useful for bacteria metabolism or internalized by intestinal cells. Thanks to their elevated structural heterogeneity, milk GAGs are used differently depending on their distinct primary structure. Finally, a different utilization and availability was observed for human milk GAGs compared to formula milk due to their various composition and structural heterogeneity.     

Effects of astaxanthin in obese mice fed a high-fat diet

Astaxanthin is a natural antioxidant carotenoid that occurs in a wide variety of living organisms. We investigated the effects of astaxanthin supplementation in obese mice fed a high-fat diet. Astaxanthin inhibited the increases in body weight and weight of adipose tissue that result from feeding a high-fat diet. In addition, astaxanthin reduced liver weight, liver triglyceride, plasma triglyceride, and total cholesterol. These results suggest that astaxanthin might be of value in reducing the likelihood of obesity and metabolic syndrome in affluent societies.     

Oxyntomodulin ameliorates glucose intolerance in mice fed a high-fat diet

We evaluated the acute effects of OXM on glucose metabolism in diet-induced insulin-resistant male C57Bl/6 mice. To determine the effects on glucose tolerance, mice were intraperitoneally injected with OXM (0.75, 2.5, or 7.5 nmol) or vehicle prior to an ip glucose tolerance test. OXM (0.75 nmol/h) or vehicle was infused during a hyperinsulinemic euglycemic clamp to quantify insulin action on glucose production and disposal. OXM dose-dependently improved glucose tolerance as estimated by AUC for glucose (OXM: 7.5 nmol, 1,564 +/- 460, P < 0.01; 2.5 nmol, 1,828 +/- 684, P < 0.01; 0.75 nmol, 2,322 +/- 303, P < 0.05; control: 2,790 +/- 222 mmol.l(-1).120 min). Insulin levels in response to glucose administration were higher in 7.5 nmol OXM-treated animals compared with controls. In basal clamp conditions, OXM increased EGP (82.2 +/- 14.7 vs. 39.9 +/- 5.7 micromol.min(-1).kg(-1), P < 0.001). During insulin infusion, insulin levels were twice as high in OXM-treated mice compared with controls (10.6 +/- 2.8 vs. 4.4 +/- 2.2 ng/ml, P < 0.01). Consequently, glucose infusion rate (118.6 +/- 30.8 vs. 38.8 +/- 26.4 microl/h, P < 0.001) and glucose disposal (88.1 +/- 13.0 vs. 45.2 +/- 6.9 micromol.min(-1).kg(-1), P < 0.001) were enhanced in mice that received OXM. In addition, glucose production was more suppressed during OXM infusion (35.7 +/- 15.5 vs. 15.8 +/- 11.4% inhibition, P < 0.05). However, if these data were expressed per unit concentration of circulating insulin, OXM did not affect insulin action on glucose disposal and production. These results indicate that OXM beneficially affects glucose metabolism in diet-induced insulin-resistant C57Bl/6 mice. It ameliorates glucose intolerance, most likely because it elevates glucose-induced plasma insulin concentrations. OXM does not appear to impact on insulin action.     

Inflammatory serum proteome pattern in mice fed a high-fat diet

To investigate the influence of diet on serum protein pattern, mice were fed for 8 weeks either control chow or a high-fat diet (containing 21 % w/w milk fat and 0.2 % w/w cholesterol); sera were collected and analyzed by 2-DE. The main positive acute-phase reactant proteins, haptoglobin and hemopexin, were significantly up-regulated in animals receiving the high-fat diet. Data on all other proteins also pointed to an inflammatory condition in these animals. The largest change in concentration was observed for carboxylesterase N, a circulating enzyme seldom connected with lipid metabolism in earlier reports. These observations agree with the notion of a link between diet-induced hyperlipidemia and the inflammatory component of its cardiovascular sequels in humans, but the effects in the experimental animals are massive and obviously affect most of the major serum proteins.     

Occurrence of bifidobacteria in faeces of calves fed milk or a combined diet

The development of faecal bacteria composition in calves fed milk or a combined diet was investigated from 4 to 21 days of age. On day 7, bifidobacteria in faeces of milk-fed calves already increased from about 7.6 to 9.2 log CFU/g and did not change until the end of the study, whereas in calves fed the combined diet bifidobacteria only moderately increased to 7.9 log CFU/g and decreased slowly until day 21. The counts of bifidobacteria in calves on a combined diet were significantly (p < 0.01) lower compared to those in milk-fed calves. Bifidobacterial counts determined by cultivation or by fluorescence in situ hybridisation (FISH) did not differ significantly. Our results showed that the occurrence of bifidobacteria in calf faeces is highly dependent on the diet composition. Faecal bacteria flora of calves fed exclusively by milk is rich in bifidobacteria, but in calves on a combined diet coliforms dominated.     

Sex specificity of myocardial damage in mice fed a purified diet

Both sexes of BALB/c and B6C3F1 mice were divided into test groups and fed either a purified diet (AIN-76A) or a natural ingredient diet (NIH-07) containing graded levels of 2-acetylaminofluorine (2-AAF) for 90 days. A large number of dead or moribund B6C3F1 males fed the AIN diet were removed from the study prematurely. AIN-fed B6C3F1 mice removed early as well as some sacrificed at the end of the study showed myocardial damage with hemorrhage. A much smaller number of BALB/c males fed the AIN diet also exhibited these signs while none of the females from either stock were affected. Mice having these lesions were confined largely to 2 of 5 treatment groups. Increased levels of serum aspartate aminotransferase (GOT) (P less than .01) occurred in the AIN-fed B6C3F1 male mice that were sacrificed, supporting the histopathological observation of myocardial damage. There was no other significant difference in the GOT between diets or 2-AAF doses. No environmental factors could be associated with the problem and microbiological and chemical analyses of the diets showed no convincing evidence of specific pathogenic organisms or nutritional deficiencies that might have caused these lesions. Extended storage (up to 4 months) and one batch of feed in particular seemed to be associated with mice having myocardial damage. These associations were highly strain and sex dependent and suggest that great care must be taken in the manufacture and handling of the diet. Furthermore, it seems likely that the diet may be marginally adequate for some strains of mice and may require modification before it will become generally useful.     

Somatostatin is involved in anorexia in mice fed a valine-deficient diet

The ingestion of a valine (Val)-deficient diet results in a significant reduction of food intake and body weight within 24 h, and this phenomenon continues throughout the period over which such a diet is supplied. Both microarray and real-time PCR analyses revealed that the expression of somatostatin mRNA was increased in the hypothalamus in anorectic mice that received a Val-deficient diet. On the other hand, when somatostatin was administered intracerebroventricularly to intact animals that were fed a control diet, their 24-h food intake decreased significantly. In addition, Val-deficient but not pair-fed mice or those fasted for 24 h showed a less than 0.5-fold decrease in the hypothalamic mRNA expression levels of Crym, Foxg1, Itpka and two unknown EST clone genes and a more than twofold increase in those of Slc6a3, Bdh1, Ptgr2 and one unknown EST clone gene. These results suggest that hypothalamic somatostatin and genes responsive to Val deficiency may be involved in the central mechanism of anorexia induced by a Val-deficient diet.     

Improved circadian sleep-wake cycle in infants fed a day/night dissociated formula milk

On the basis of the circadian nutritional variations present in breast milk, and of the implications for the sleep/wake cycle of the nutrients present in infant formula milks, we designed a formula milk nutritionally dissociated into a Day/Night composition. The goal was to improve the bottle-fed infant's sleep/wake circadian rhythm. A total of 21 infants aged 4-20 weeks with sleeping difficulties were enrolled in the three-week duration study. The sleep analysis was performed using an actimeter (Actiwatch) placed on an ankle of each infant to uninterruptedly record movements during the three weeks. The dissociated Day milk, designed to be administered from 06:00 to 18:00, contained low levels of tryptophan (1.5g/100g protein) and carbohydrates, high levels of proteins, and the nucleotides Cytidine 5 monophosphate, Guanosine 5 monophosphate and Inosine 5 monophosphate. The dissociated Night milk, designed to be administered from 18.00 to 06.00, contained high levels of tryptophan (3.4g/100g protein) and carbohydrates, low levels of protein, and the nucleotides Adenosine 5 monophosphate and Uridine 5 monophosphate. Three different milk-feeding experiments were performed in a double-blind procedure covering three weeks. In week 1 (control), the infants received both by day and by night a standard formula milk; in week 2 (inverse control), they received the dissociated milk inversely (Night/Day instead of Day/Night); and in week 3, they received the Day/Night dissociated formula concordant with the formula design. When the infants were receiving the Day/Night dissociated milk in concordance with their environment, they showed improvement in all the nocturnal sleep parameters analyzed: total hours of sleep, sleep efficiency, minutes of nocturnal immobility, nocturnal awakenings, and sleep latency. In conclusion, the use of a chronobiologically adjusted infant formula milk seems to be effective in improving the consolidation of the circadian sleep/wake cycle in bottle-fed infants.     

Energy balance and facultative diet-induced thermogenesis in mice fed a high-fat diet

The present study was aimed at studying energy balance in mice fed a high-fat diet. Albino mice were divided into three groups. One group had free access to the stock diet, whereas the two other groups consumed a high-fat diet. One of the high-fat fed groups was fed ad libitum, whereas the other was offered a restricted amount of the same diet so that its energy intake was comparable to the group of mice given the stock diet. Energy balance measurements, which included indirect calorimetry and carcass analysis, were performed. Brown adipose tissue (BAT) properties were also investigated. The results show that gains in both body weight and fat were higher in mice that had free access to high-fat diet than in mice fed the stock diet. In animals given a restricted amount of the high-fat diet, fat gain increased, whereas protein gain was reduced in comparison with animals fed the stock diet. Unrestricted access to the high-fat diet led to an increase in both energy intake and energy gain. As revealed by both slaughter and indirect calorimetry techniques energy expenditure was, in high-fat fed mice, 40% higher than in animals fed either stock or a restricted amount of high-fat diet. Nadolol was shown to suppress a large part of the elevated metabolic rate seen in mice fed an unrestricted high-fat diet. In those mice, BAT mitochondrial GDP binding was also increased. In summary, the present results confirm that adaptive diet-induced thermogenesis (DIT) develops in mice made hyperphagic by an energy-dense palatable diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Egg and cows' milk hypersensitivity in exclusively breast fed infants with eczema,and detection of egg protein in breast milk.

Forty nine eczematous infants who were still solely and exclusively breast fed and who had never received anything but breast milk were studied for evidence of sensitisation to foods. Thirty four similar infants without eczema formed a control group. The eczematous infants were divided into three groups according to clinical criteria: (1) definite atopic eczema; (2) possible atopic eczema; (3) atopic eczema unlikely. Twenty three infants showed cutaneous hypersensitivity to foods, usually egg and cows'' milk. Seven of 14 infants in group 1 and nine of 20 in group 2 were sensitised compared with four of 15 in group 3 and three of 34 controls (p less than 0.01). Ovalbumin was detected in breast milk from 14 of 19 mothers tested after ingestion of egg, the concentrations being the same for mothers feeding eczematous and normal infants. Breast fed babies developing eczema may be sensitised by foods eaten by their mothers.     

Effects of dietary sewage solids on second-generation ewes fed an experimental diet from weaning through two reproductive cycles

Eighteen fine-wool ewe lambs produced by mature, conventionally fed dams and 21 similar offspring from sewage-fed ewes were randomly allotted at weaning to one of two groups. Half of the lambs from each maternal diet group received a conventional (18% protein) diet during the growing phase while the remainder was fed the conventional diet plus 7% undigested, irradiated sewage solids (18% protein). At the end of the 147-day growing period and just before a fall breeding season, conventionally fed ewe lambs were switched to a control diet (12% protein) suitable for mature ewes and sewage-fed ewe lambs began receiving the control diet plus 7% sewage solids. Animals received these diets for two years. Maternal sewage consumption did not influence performance of F₁ ewe lambs. By the beginning of the first breeding season, controls were heavier (P<0.01) than were animals receiving sewage solids (51.7 and 44.5 kg, respectively). Similarly, only 75% of sewage-fed ewe lambs exhibited estrus during their first breeding season compared with 94.7% of controls (P<0.10). Conception rate (40.0 and 84.2%, respectively) and lambs born per ewe exposed (0.4 and 0.89, respectively) were also lower (P<0.05) in animals receiving sewage solids than in controls. During the second reproductive cycle, conception rate as well as lambs born per ewe exposed was comparable (P>0.10) between the two groups. Offspring from the sewage-fed ewe lambs, however, weighed less (P<0.05) at weaning than did lambs produced by control animals. Results indicate that a diet containing 7% sewage solids may not be suitable for preparing ewe lambs to go into the breeding flock; once mature size is attained, however, reproductive performance is not hampered by sewage feeding.     

Serum and milk concentrations of leptin in gilts fed a high- or low-energy diet during gestation

Concentrations of leptin in serum and milk were assessed in gilts fed diets during gestation that differed in energy level. Beginning at day 45 and continuing throughout pregnancy, gilts received either a high-energy (6882 kcal metabolizable energy (ME) per day) or low-energy (5221 kcal ME per day) diet (n = 9 per group). All gilts had ad libitum access to a standard lactation diet throughout a 21 day lactation. During gestation, gilts consuming the high-energy diet gained more body weight (P < 0.01) and backfat thickness (P = 0.03) than gilts fed the low-energy diet; however, serum concentrations of leptin remained similar between groups (P = 0.35). Within 24 h after farrowing, gilts fed the high-energy diet had greater levels of leptin in serum and milk than gilts that consumed the low-energy diet during gestation (P < 0.07); Across treatments, backfat thickness and leptin levels in serum were positively correlated (r(2) = 0.51; P = 0.03). At weaning, backfat thickness (P < 0.07), but not body weights or serum and milk levels of leptin (P > 0.1), were greater for gilts fed the high-energy, versus the low-energy, diet during gestation. Gilts that were fed the low-energy diet during gestation consumed more feed during week 2 of lactation (P = 0.06). Our results suggest that altering the level of energy in the diets of gestating swine can influence circulating and milk concentrations of leptin, as well as feed consumption, during lactation.     

Vitamin E modulates radiation-induced oxidative damage in mice fed a high-lipid diet

The Vitamin E (VE) effect was examined on oxidative damage to DNA, lipids, and protein in mice that were fed various levels of lipid diets after total body irradiation (TBI) with X-rays at 2 Gy. No increase of 8-hydroxydeoxyguanosine (8OHdG) by TBI was observed in the + VE group; however, in the case of the -VE group, a significantly higher 8OHdG level was observed in the high-lipid group than in the low- or basal-lipid group. In the groups with TBI, the concentration of thiobarbituric reactive substances (TBARS) only significantly increased in the high-lipid (-VE) group. These changes in TBARS, due to TBI, were not detected in other groups. The contents of protein carbonyls only increased in the (-VE) group. The contents of protein carbonyls was significantly different between the (+VE) and the (-VE) groups, regardless of the lipid levels. The concentrations of GSH, vitamins C and E in the liver were lower, and the concentration of non-heme iron in the liver was higher in the high-lipid group than in the low- and basal-lipid groups. These concentrations in the high-lipid group were significantly different between the (+VE) and the (-VE) groups. These results strongly suggest that mice that are fed a high-lipid diet are susceptible to TBI-induced oxidative damage. Also, decreases in the GSH levels and an increase in the iron level are involved in the mechanism of this susceptibility.     

Changes in the small intestine of Schistosoma mansoni-infected mice fed a high-fat diet

The consumption of a high-fat diet modifies both the morphology of the small intestine and experimentally tested effects of schistosomiasis mansoni. However, whether a schistosomiasis infection associated with a high-fat diet causes injury to the small intestine has never been investigated. Mice were fed either a high-fat or a standard-fat diet for 6 months and were then infected with Schistosoma mansoni cercariae. Physical characteristics of the intestinal tissue (mucosal thickness, small intestinal villi length and height, and abundance of goblet cells and enterocytes on the villous surface) and the distribution of granulomas along the intestinal segments and their developmental stage were measured at the time of sacrifice (9 or 17 weeks post-infection). The group fed a high-fat diet exhibited different granuloma stages, whereas the control group possessed only exudative granulomas. The chronically infected mice fed a high-fat diet exhibited higher granuloma and egg numbers than the acutely infected group. Exudative, exudative/exudative-productive and exudative-productive granulomas were present irrespective of diet. Computer-aided morphometric analysis confirmed that villus length, villus width, muscular height and submucosal height of the duodenal and jejunal segments were affected by diet and infection. In conclusion, a high-fat diet and infection had a significant impact on the small intestine morphology and morphometry among the animals tested.     

The effect of taurine on cholesterol degradation in mice fed a high-cholesterol diet

The hypocholesterolemic effect of taurine was examined in mice fed a high-cholesterol diet containing 1% cholesterol and 0.25% sodium cholate. Male C57BL/6 mice were divided into 3 groups: control group (HC), 1% taurine-supplemented group (HCT+), and taurine-deficient group (HCT-) produced by supplying 0.5% guanidinoethyl sulfonate (GES) solution ad libitum instead of water. After they were fed with the respective diet or drinking water for 4 weeks, the liver taurine level was reduced 80% in the HCT- group compared with that in the HC group, although there was no difference in the serum taurine amount between the two groups. The formation ratio of cholesterol gallstones increased from 71% to 100% by taurine deficiency, and decreased to 0% by taurine supplementation. Compared with the HC group, serum and liver cholesterol significantly decreased, and the excretion of fecal bile acid notably rose in the HCT+ group but tended to lower in the HCT- group. There were no differences in LDL receptor protein level among the three groups. In the subsequent experiment, triglycerides (TG) secretion rate was determined and found to be significantly suppressed by taurine supplementation. In conclusion, it is suggested that taurine does not up-regulate LDL receptor protein level, and the decrease in cholesterol in the circulation is mainly due to its suppressive effect on TG secretion from the liver.     

Steatohepatitis develops rapidly in transgenic mice overexpressing Abcb11 and fed a methionine-choline-deficient diet

Nonalcoholic fatty liver disease is the most common reason for abnormal liver chemistries in the United States. The factors that lead from benign steatosis to nonalcoholic steatohepatitis are poorly understood. Transthyretin-Abcb11 (TTR-Abcb11) transgenic mice overexpress the bile salt transporter Abcb11 and hypersecrete biliary lipids. Thus the aim of this study is to employ feeding of the methionine-choline-deficient (MCD) diet to TTR-Abcb11 transgenic mice to further determine the mechanisms responsible for the development of steatohepatitis. FVB/NJ and TTR-Abcb11 mice were fed control or MCD diets for up to 30 days. Serum aminotransferase levels, serum and hepatic triglyceride content, cytokines, markers of oxidative stress, and expression of selective genes were examined. MCD diet-fed TTR-Abcb11, but not wild-type, mice have elevated serum aminotransferase levels when compared after 7 days. They also have significantly lower hepatic triglyceride levels at all time points studied. After 14 days on the MCD diet, TTR-Abcb11 mice have 3-fold increases in TNF-alpha mRNA and 3.9-fold increases in IL-6 mRNA compared with FVB/NJ mice. TTR-Abcb11 mice also had a greater increase in cytochrome P-450 2E1 expression. A greater decrease in sterol regulatory element binding protein-1c and fatty acid synthase mRNA expression was also seen in TTR-Abcb11 compared with wild-type mice fed an MCD diet. They also have enhanced TNF-alpha, IL-6, and cytochrome P-450 2E1 expression. We conclude that TTR-Abcb11 mice develop a more rapid hepatitis with less steatosis.